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To maximize the probability of survival, cells need to coordinate their intracellular activities in response to changes in the extracellular environment. MAP kinase cascades play an important role in the transduction of signals inside eukaryotic cells. In particular, stress stimuli result in the rapid activation of a highly conserved group of MAP kinases, known as SAPKs (Stress-Activated Protein Kinases). These kinases coordinate the generation of adaptive responses that are essential for cell survival, which include the modulation of several aspects of cell physiology from metabolism to gene expression.

In this book, leading researchers in the field discuss the state-of-the-art of many aspects of SAPK signalling in various systems from yeast to mammals. These include various chapters on regulatory mechanisms as well as the contribution of the SAPK signalling pathways to processes such as gene expression, metabolism, cell cycle regulation, immune responses and tumorigenesis.

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Product Details

  • ISBN-13: 9783540755685
  • Publisher: Springer Berlin Heidelberg
  • Publication date: 2/25/2008
  • Series: Topics in Current Genetics Series , #20
  • Edition description: 2008
  • Edition number: 1
  • Pages: 312
  • Product dimensions: 6.30 (w) x 9.40 (h) x 0.90 (d)

Table of Contents

MAPK kinase kinase regulation of SAPK/JNK pathways   Lisa Stalheim   Gary L. Johnson     1
Abstract     1
Introduction     1
Organization of the MKKK-MKK4/7-JNK1/2/3 signaling module     3
MKKKs as signaling hubs controlling JNK activation     4
MLKs (mixed lineage kinases)     5
MEKKs (MAPK-ERK kinase kinases)     5
ASK1 (apoptosis signal-regulating kinase 1)     6
TAK1 (TGF[beta]-activated kinase 1)     6
TAO1 (thousand and one-amino acid kinase 1)     6
Insight into the function of MKKKs regulating the JNK pathway from targeted gene knockouts     7
MEKK1     7
MEKK2     8
MEKK4     9
ASK1     9
TAK1     10
MLK3     10
Conclusions     10
References     11
Alternative p38 MAPK pathways   Francisco Inesta-Vaquera   Guadalupe Sabio   Yvonne Kuma   Ana Cuenda     17
Abstract     17
Introduction     17
The p38[gamma] and p38[delta] MAPK pathways     19
p38[gamma] and p38[delta] substrates     20
Biological roles of p38[gamma] and p38[delta]MAPK pathways     21
Cell cycle and cellular transformation     21
Cellular differentiation     22
Cytoskeletal organization     24
More alternative p38MAPK pathways?     25
Concluding remarks     25
Acknowledgments     26
References     26
The regulation of stress-activated MAP kinase signalling by protein phosphatases   Stephen M. Keyse     33
Abstract     33
Introduction     33
Regulation of stress-activated MAPKs by protein phosphatases in S. cerevisiae     34
Regulation of JNK and p38 MAPKs in Drosophila and C. elegans     37
The Drosophila phosphatase puckered plays key roles in development, stress responses and ageing     37
The vhp-1 phosphatase plays key roles in regulating stress responses and immunity in C. elegans     37
Mammalian MKPs play essential roles in the regulation of both JNK and p38 MAP kinase signalling     39
A subset of mammalian MKPs can regulate stress-activated MAPK pathways     39
DUSP10/MKP-5 plays a key role in adaptive and innate immunity     39
Inducible nuclear MKPs play key roles in stress resistance, immune function, and metabolic homeostasis     41
DUSP1/MKP-1 is a key regulator of stress resistance      41
DUSP1/MKP-1 regulates both immune and metabolic function     42
DUSP2/PAC-1 is a positive regulator of certain inflammatory responses     43
Summary     44
Acknowledgements     45
References     45
Transcriptional regulation by the p38 MAPK signaling pathway in mammalian cells   Eusebio Perdiguero   Pura Munoz-Canoves     51
Abstract     51
Transcription in mammalian cells     51
Regulatory DNA elements     52
Chromatin modifying activities     52
Transcription factors     52
The p38 MAPK signaling pathway     53
MAPK pathways     53
p38 MAPKs     53
Upstream kinases     53
Downstream substrates     54
Downregulators     57
Consequences of p38 MAPK activation on growth and differentiation of mammalian cells     57
Skeletal muscle proliferation and differentiation     58
Adipocyte differentiation     61
Cardiomyocyte hypertrophy     65
Conclusions and perspectives     68
Acknowledgements     70
References     70
Regulation of gene expression in response to osmostress by the yeast stress-activated protein kinase Hog1   Eulalia de Nadal   Francesc Posas     81
Abstract     81
Introduction     81
Regulation of HOG signaling     82
The Hog1 MAPK as a central component of transcription activation upon osmostress     84
Transcriptional regulators downstream of the HOG pathway     84
The bZIP protein Sko1     85
The MADS box protein Smp1     85
The zinc finger proteins Msn2 and Msn4     86
The Hot1 transcription factor     86
Hog1 is part of the transcription complexes at the promoters of osmostress genes     87
Regulation of chromatin remodeling by the Hog1 MAPK     88
Hog1 MAPK and transcription elongation     89
Conclusions and perspectives     90
Acknowledgement     92
References     92
Regulation of tumorigenesis by p38[alpha] MAP kinase   Ignacio Dolado   Angel R. Nebreda     99
Abstract     99
Introduction     99
Cell cycle regulation     100
Inhibition of the G1/S transition     101
Inhibition of the G2/M transition     101
Stimulation of cell cycle progression     103
Regulation of cell survival and apoptosis     104
Apoptosis induction     107
Anti-apoptotic roles     108
Reconciling pro- and anti-apoptotic functions     110
Regulation of cell differentiation     111
Inflammation     112
Cell migration and invasion     113
Concluding remarks     114
Acknowledgments     115
References     115
List of abbreviations     128
Control of cell cycle by SAPKs in budding and fission yeast   Sandra Lopez-Aviles   Rosa M. Aligue     129
Abstract     129
Introduction     129
Cell cycle control by SAPKs in Saccharomyces cerevisiae     130
Cell cycle regulation     130
Stress-activated protein kinase pathway and cell cycle control     130
Cell cycle control by SAPKs in Schizosaccharomyces pombe     132
Cell cycle regulation     132
Stress-activated protein kinase pathway and cell cycle control     133
Concluding remarks     136
Acknowledgements     137
References     137
Hog1-mediated metabolic adjustments following hyperosmotic shock in the yeast Saccharomyces cerevisiae   Bodil Nordlander   Marcus Krantz    Stefan Hohmann     141
Abstract     141
Yeast osmoregulation and carbon metabolism     141
Osmolytes: glycerol and trehalose as cell protectants     144
Flux control and potential direct effects on metabolism by Hog1: PFK2     147
Glycerol export and import     151
Integration: a potential timeline of adjustments under osmo-stress     153
Acknowledgements     153
References     153
Control of mRNA stability by SAPKs   Miguel A. Rodriguez-Gabriel   Paul Russell     159
Abstract     159
Introduction     159
Eukaryotic mRNA turnover     160
Proteins involved     160
Localization     161
mRNA cis acting elements     162
Control of mRNA stability by SAPKs     162
RNA binding proteins involved in SAPK regulation of mRNA stability     163
Concluding remarks     165
Acknowledgement     166
References     166
Intrinsically active (MKK- independent) variants of SAPKs - How do they work?   Inbal Maayan   David Engelberg     171
Abstract     171
Introduction     171
Intrinsically active variants of SAPKs - bypassing their natural mode of activation     173
Mechanism of activation of native SAPKs and of intrinsically active SAPKs     176
The role of the phosphoacceptors in the intrinsically active variants     176
The mutants acquired an auto-phosphorylation capability     178
Structural changes due to activation     179
Discussion     180
References     182
Regulation of MAPK signaling in yeast   Fabian Rudolf   Serge Pelet   Matthias Peter     187
Abstract     187
Introduction to MAPK signaling during mating and high osmolarity conditions in yeast     187
Quantifying signaling at the single cell level     189
Regulation of mating signaling     191
Pathway activation     191
Spatial/temporal regulation     193
Regulation of mating signaling by internal and external factors     196
The Osmotic stress pathway     197
Pathway activtion by stress signals     197
Internal regulation of the HOG pathway     198
Specificity/crosstalk between the two pathways     199
General principles for yeast MAPK regulation     199
Single cell measurement - future research      200
Acknowledgments     201
References     201
Modeling the dynamics of stress activated protein kinases (SAPK) in cellular stress response   Edda Klipp   Jorg Schaber     205
Abstract     205
Introduction     205
Mathematical modeling in systems biology     206
Purpose of modeling     206
Model development in five steps     206
Mathematical modeling of biochemical reaction networks     209
Analysis of models     212
Studied phenomena     214
Dynamic behavior and parameters     214
Ultrasensitivity, amplification, and robustness     216
Relative importance of kinases and phosphatases     217
Regulation of MAPK cascade by receptor activity     218
Regulation of MAPK cascade by downstream processes - feedback     219
Crosstalk and dynamics     220
Discussion/Summary     221
Acknowledgement     221
References     222
Stress-activated protein kinase signaling in Drosophila   Gerasimos P. Sykiotis   Dirk Bohmann     225
Abstract     225
Introduction     225
Structural conservation of the JNK and p38 pathways in Drosophila     226
JNK signaling in Drosophila     228
Morphogenesis, wound healing, and immunity     228
Oxidative stress defense and lifespan regulation     229
JNK-dependent apoptosis during development     229
JNK in TNF- and irradiation-induced apoptosis     230
p38 signaling in Drosophila     232
Identification of the fruit fly p38 homologues     232
p38 in Drosophila development     232
Genetic analysis of the fruit fly p38 pathway     234
RNA interference in cultured Drosophila cells     235
Downstream effectors and upstream components of Drosophila p38 signaling     236
Outlook     237
References     237
Protein kinases as substrates for SAPKs   Alexey Kotlyarov   Matthias Gaestel     243
Abstract     243
Definition of kinases downstream to SAPKs     243
Primary structure and overview     245
SAPK-regulated kinases in detail     245
MSKs     245
MNKs     248
MK2/3     251
Summary and Perspectives     253
Acknowledgement     253
References     253
List of abbreviations     260
Functions of stress-activated MAP kinases in the immune response   Mercedes Rincon   Roger J. Davis     261
Abstract     261
Introduction     261
SAPK Functions in macrophages and dendritic cells     261
Role of JNK     261
Role of p38 MAPK     263
SAPK functions in B cells     264
Role of JNK     264
Role of p38 MAPK     264
SAPK Functions in T cell development     265
Role of JNK     265
Role of p38 MAPK     265
SAPK functions in CD4[superscript +] T cells     266
Role of JNK     266
Role of p38 MAPK     268
SAPK functions in CD8[superscript +] T cells     269
Role of JNK     269
Role of p38 MAPK     271
SAPK functions in other T cell populations     272
SAPK functions during an in vivo immune response     273
Concluding remarks     275
References     275
Stress-activated MAP kinases in chromatin and transcriptional complexes   Nicholas T. Crump   Ya Ting Han   Louis C. Mahadevan     283
Abstract      283
Introduction     283
SAPK cascades in yeast and mammals     284
Phosphorylation of sequence-specific transcription factors and recruitment of histone-modifying enzymes     286
Phosphorylation of general transcription factors     288
Phosphorylation of nucleosomal proteins     288
Inducible histone H3 phosphorylation is mediated by MSK1/2     289
Molecular function of histone H3 phosphorylation     290
SAPKs may also act independently of their kinase activity     291
A role for mammalian SAPKs in transcriptional and elongation complexes?     293
Concluding remarks     293
References     294
SAPK and translational control   Malin Hult   Per Sunnerhagen     299
Abstract     299
Background and paradigms for control of translation     299
Global controls of translation     300
Global control of initiation by phosphorylation of eIF2[alpha]     300
Global control of initiation by phosphorylation of eIF4E/4E-BP     300
Global control of elongation     301
Individual control of mRNA species - AREs     302
ARE-binding proteins under SAPK control     303
MAPK-activated protein kinases in signalling through AREs      303
Links between translation and mRNA degradation     304
IRES     304
Indirect effects on translation through transcriptional and posttranscriptional regulation     305
Concluding remarks     306
Acknowledgements     307
References     307
Index     311
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